ArticleProceedings of the National Academy of Sciences of the United States of America2019
Mitochondrial transcription factor A promotes DNA strand cleavage at abasic sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Mitochondrial DNA leakage in oocytes activates cGAS-STING signaling to drive ovarian aging.Nature aging · 2026Article
- Article
- Mitochondrial DNA in systemic lupus erythematosus: pathogenic mechanisms, clinical biomarkers, and precision therapeutic strategies.Frontiers in immunology · 2026Review
- Mitochondrial transcription factor A: linking mtDNA maintenance, mitochondrial stress responses, and inflammaging.Frontiers in aging · 2026Review
- Glutathionylated DNA adducts accumulate in mitochondrial DNA and are regulated by AP endonuclease 1 and tyrosyl-DNA phosphodiesterase 1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mitochondria-Targeting Abasic Site-Reactive Probe (mTAP) Enables the Manipulation of Mitochondrial DNA Levels.Angewandte Chemie (International ed. in English) · 2025Article
- Methods for Mitochondrial DNA Damage and Depletion in Immortalized Trabecular Meshwork Cells.International journal of molecular sciences · 2025Article
- Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis.Chembiochem : a European journal of chemical biology · 2025Review
- The Hallmarks of Ageing in Microglia.Cellular and molecular neurobiology · 2025Review
- Targeted deletions in human mitochondrial DNA engineered by Type V CRISPR-Cas12a system.NAR molecular medicine · 2025Article
- DNA repair pathways in the mitochondria.DNA repair · 2025Review
- Mechanisms underlying targeted mitochondrial therapy for programmed cardiac cell death.Frontiers in physiology · 2025Review
- DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products.Nucleic acids research · 2024Article
- Dexamethasone Impairs ATP Production and Mitochondrial Performance in Human Trabecular Meshwork Cells.Current issues in molecular biology · 2024Article
- Mitochondrial transcription factor A (TFAM) has 5'-deoxyribose phosphate lyase activity in vitro.DNA repair · 2024Article
- Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production.International journal of molecular sciences · 2024Article
- Dual chemical labeling enables nucleotide-resolution mapping of DNA abasic sites and common alkylation damage in human mitochondrial DNA.Nucleic acids research · 2023Article
- 35 Years of TFAM Research: Old Protein, New Puzzles.Biology · 2023Review
- Key Amino Acid Residues of Mitochondrial Transcription Factor A Synergize with Abasic (AP) Site Dynamics To Facilitate AP-Lyase Reactions.ACS chemical biology · 2023Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
In higher eukaryotic cells, mitochondria are essential subcellular organelles for energy production, cell signaling, and the biosynthesis of biomolecules. The mitochondrial DNA (mtDNA) genome is indispensable for mitochondrial function because it encodes protein subunits of the electron transport chain and a full set of transfer and ribosomal RNAs. MtDNA degradation has emerged as an essential quality control measure to maintain mtDNA and to cope with mtDNA damage resulting from endogenous and environmental factors. Among all types of DNA damage known, abasic (AP) sites, sourced from base excision repair and spontaneous base loss, are the most abundant endogenous DNA lesions in cells. In mitochondria, AP sites trigger rapid DNA loss; however, the mechanism and molecular factors involved in the process remain elusive. Herein, we demonstrate that the stability of AP sites is reduced dramatically upon binding to a major mtDNA packaging protein, mitochondrial transcription factor A (TFAM). The half-life of AP lesions within TFAM-DNA complexes is 2 to 3 orders of magnitude shorter than that in free DNA, depending on their position. The TFAM-catalyzed AP-DNA destabilization occurs with nonspecific DNA or mitochondrial light-strand promoter sequence, yielding DNA single-strand breaks and DNA-TFAM cross-links. TFAM-DNA cross-link intermediates prior to the strand scission were also observed upon treating AP-DNA with mitochondrial extracts of human cells. In situ trapping of the reaction intermediates (DNA-TFAM cross-links) revealed that the reaction proceeds via Schiff base chemistry facilitated by lysine residues. Collectively, our data suggest a novel role of TFAM in facilitating the turnover of abasic DNA.
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